1. Anakinra Drugbank ID : DB00026
Protein chemical formula : C759H1186N208O232S10
Protein average weight :
Half life : Healthy subjects = hours;
NOMID patients = 5.7 hours (range of hours).

2. Description : Indication :
Anakinra is a recombinant, nonglycosylated human interleukin-1 receptor antagonist (IL-1Ra). The difference between anakinra and the native human IL-1Ra is that anakinra has an extra methionine residue at the amino terminus. It is manufactured by using the E. coli expression system. Anakinra is composed of 153 amino acid residues. FDA approved on November 14, 2001.
Indication :
For the treatment of adult rheumatoid arthritis and treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID).

3. Pharmacodynamics :
Used to treat rheumatoid arthritis, Anakinra blocks the biologic activity of IL-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Patients with rheumatoid arthritis have elevated levels of IL-1. The levels of the naturally occurring IL-1Ra in synovium and synovial fluid from rheumatoid arthritis (RA) patients are not sufficient to compete with the elevated amount of locally produced IL-1. Increasing the levels of IL-1Ra by artificial means reduces the negative effects (cartilage degradation, bone resorption) of IL-1.

4. Mechanism of action : Absorption :
Anakinra binds competitively to the Interleukin-1 type I receptor (IL-1RI), thereby inhibiting the action of elevated levels IL-1 which normally can lead to cartilage degradation and bone resorption. .
Absorption :
When a 70 mg subcutaneous bolus injection is given to healthy subjects, the absolute bioavailability is 95%. Accumulation does not occur following daily subcutaneous doses. Tmax, SubQ, 1-2 mg/kg, healthy subjects = 3-7 hours; Cmax, SubQ, 3 mg/kg once daily, NOMID patients = 3628 ng/mL.

5. Clearance :
Clearance is variable and increases with increasing creatinine clearance and body weight. However, gender and age were not significant factors.
Toxicity :
Most common adverse reactions (incidence ≥ 5%) are injection site reaction, worsening of rheumatoid arthritis, upper respiratory tract infection, headache, nausea, diarrhea, sinusitis, arthralgia, flu like-symptoms, and abdominal pain when anakinra is used in RA patients. In NOMID patients, the most common AEs during the first 6 months of treatment (incidence >10%) are injection site reaction, headache, vomiting, arthralgia, pyrexia, and nasopharyngitis.

6. Drug Interaction: Targets : Affected organisms :
Abatacept : Avoid combination due to enhanced adverse effects of abatacept
Canakinumab : results in increased immunosuppressive effects; increases the risk of infection.
Certolizumab pegol : Co-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
Etanercept : Avoid combination due to increased adverse effects of anakinra and increased risk of infections.
Golimumab : Avoid combination with anakinra due to the increased chance of serious infection. Infliximab : Combination may enhance the toxic effect of Anakinra and should be avoided otherwise there may be an increased risk of infection
Rilonacept : results in increased immunosuppressive effects; increases the risk of infection. Thalidomide : Thalidomide may increase the adverse effects of Anakinra. Increased risk of serious infection. Concomitant therapy should be avoided.
Tofacitinib : Avoid combination due to the potential increase in tofacitinib related adverse effects. Trastuzumab : Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Targets :
Interleukin-1 receptor type 1
Affected organisms :
Humans and other mammals .

7. Categories : Patents : Sequence :
Antirheumatic Agents and Immunosuppressive Agents
Patents :
Country Patent Number Approved Expires
Canada
Canada
Sequence :
MRPSGRKSSKMQAFRIWDVNQKTFYLRNNQLVAGYLQGPNVNLEEKIDVVPIEPHALFLGIHGGKMCLSCVKSGDETRLQLEAVNITDLSENRKQDKRFAFIRSDSGPTTSFESAACPGWFLCTAMEADQPVSLTNMPDEGVMVTKFYFQEDE

8. Brands : Kineret
Company : Amgen Inc
Description : Kineret (anakinra) is a recombinant, nonglycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra). Kineret differs from native human IL-1Ra in that it has the addition of a single methionine residue at its amino terminus. Kineret consists of 153 amino acids and has a molecular weight of 17.3 kilodaltons. It is produced by recombinant DNA technology using an E coli bacterial expression system.
Used for/Prescribed for : Kineret is used to treat the symptoms of moderate to severe rheumatoid arthritis in adults. Anakinra may also help slow the progress of the disease.
Formulation : The solution may contain trace amounts of small, translucent-to-white amorphous proteinaceous particles. Each prefilled glass syringe contains: 0.67 mL (100 mg) of anakinra in a solution (pH 6.5) containing disodium EDTA (0.12 mg), sodium chloride (5.48 mg), anhydrous citric acid (1.29 mg), and polysorbate 80 (0.70 mg) in Water for Injection, USP.
Form : sterile, clear, colorless-to-white, preservative free solution
Route of administration : subcutaneous (SC) administration

9. Dosage : The recommended dose of Kineret for the treatment of patients with rheumatoid arthritis is 100 mg/day administered daily Contraindication : contraindicated in patients with known hypersensitivity to E coli-derived proteins, Kineret, or any components of the product Side effects : nausea, diarrhea, stomach pain; headache; cold symptoms such as stuffy nose, sneezing, sore throat; Drug interaction : A total of 231 drugs (750 brand and generic names) are known to interact with Kineret (anakinra) major drug interactions (64 brand and generic names) moderate drug interactions (616 brand and generic names) minor drug interactions (70 brand and generic names)

10. General references :
# Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res Jan 1;30(1): "Pubmed":
# Lequerré T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job-Deslandre C, Fautrel B, Le Loët X, Sibilia J; Société Francophone pour la Rhumatologie et les Maladies Inflammatoires en Pédiatrie (SOFREMIP); Club Rhumatismes et Inflammation (CRI): Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis Mar;67(3):281-2."Pubmed":
# FDA label

11. References :